Browsing by Author "Lougaris, Vassilios"

Now showing 1 - 3 of 3

Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase delta syndrome 2: A cohort study
(Mosby-Elsevier, 2016-07) Elkaim, Elodie; Neven, Benedicte; Bruneau, Julie; Mitsui-Sekinaka, Kanako; Stanislas, Aurelie; Heurtier, Lucie; Lucas, Carrie L.; Matthews, Helen; Deau, Marie-Celine; Sharapova, Svetlana; Curtis, James; Reichenbach, Janine; Glastre, Catherine; Parry, David A.; Arumugakani, Gururaj; McDermott, Elizabeth; Yamashita, Motoi; Moshous, Despina; Lamrini, Hicham; Otremba, Burkhard; Gennery, Andrew; Coulter, Tanya; Quinti, Isabella; Stephan, Jean-Louis; Lougaris, Vassilios; Brodszki, Nicholas; Barlogis, Vincent; Asano, Takaki; Galicier, Lionel; Boutboul, David; Nonoyama, Shigeaki; Cant, Andrew; Imai, Kohsuke; Picard, Capucine; Nejentsev, Sergey; Molina, Thierry Jo; Lenardo, Michael; Savic, Sinisa; Cavazzana, Marina; Fischer, Alain; Durandy, Anne; Kracker, Sven; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı/Çocuk İmmünoloji Bilim Dalı.; 0000-0001-8571-2581; AAH-1658-2021; 34975059200
Background: Activated phosphoinositide 3-kinase delta syndrome (APDS) 2 (p110 delta-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency [PASLI]-R1), a recently described primary immunodeficiency, results from autosomal dominant mutations in PIK3R1, the gene encoding the regulatory subunit (p85 alpha, p55 alpha, and p50 alpha) of class IA phosphoinositide 3-kinases. Objectives: We sought to review the clinical, immunologic, and histopathologic phenotypes of APDS2 in a genetically defined international patient cohort. Methods: The medical and biological records of 36 patients with genetically diagnosed APDS2 were collected and reviewed. Results: Mutations within splice acceptor and donor sites of exon 11 of the PIK3R1 gene lead to APDS2. Recurrent upper respiratory tract infections (100%), pneumonitis (71%), and chronic lymphoproliferation (89%, including adenopathy [75%], splenomegaly [43%], and upper respiratory tract lymphoid hyperplasia [48%]) were the most common features. Growth retardation was frequently noticed (45%). Other complications were mild neurodevelopmental delay (31%); malignant diseases (28%), most of them being B-cell lymphomas; autoimmunity (17%); bronchiectasis (18%); and chronic diarrhea (24%). Decreased serum IgA and IgG levels (87%), increased IgM levels (58%), B-cell lymphopenia (88%) associated with an increased frequency of transitional B cells (93%), and decreased numbers of naive CD4 and naive CD8 cells but increased numbers of CD8 effector/memory T cells were predominant immunologic features. The majority of patients (89%) received immunoglobulin replacement; 3 patients were treated with rituximab, and 6 were treated with rapamycin initiated after diagnosis of APDS2. Five patients died from APDS2-related complications. Conclusion: APDS2 is a combined immunodeficiency with a variable clinical phenotype. Complications are frequent, such as severe bacterial and viral infections, lymphoproliferation, and lymphoma similar to APDS1/PASLI-CD. Immunoglobulin replacement therapy, rapamycin, and, likely in the near future, selective phosphoinositide 3-kinase delta inhibitors are possible treatment options.
Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome
(Academic Press Inc Elsevier Science, 2011-04) Mazza, Cinzia; Buzi, Fabio; Ortolani, Federica; Vitali, Alberto; Notarangelo, Lucia D.; Weber, Giovanna; Bacchetta, Rosa; Soresina, Annarosa; Lougaris, Vassilios; Greggio, Nella A.; Taddio, Andrea; Pasic, Srdjan; de Vroede, Monique; Pac, Malgorzata; Özden, Sanal; Rusconi, Roberto; Martino, Silvana; Capalbo, Donatella; Salerno, Mariacarolina; Pignata, Claudio; Radetti, Giorgio; Maggiore, Giuseppe; Plebani, Alessandro; Notarangelo, Luigi D.; Badolato, Raffaele; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Pediatri Anabilim Dalı.; 0000-0001-8571-2581; AAH-1658-2021; 34975059200
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED.
The extended clinical phenotype of 64 patients with dedicator of cytokinesis 8 deficiency
(Mosby-Elsevier, 2015-08-01) Engelhardt, Karin R.; Gertz, Michael E.; Keleş, Sevgi; Schaeffer, Alejandro A.; Sigmund, Elena C.; Glocker, Cristina; Saghafi, Shiva; Pourpak, Zahra; Ceja, Ruben; Sassi, Atfa; Graham, Laura E.; Massaad, Michel J.; Mellouli, Fethi; Ben-Mustapha, Imen; Khemiri, Monia; Kılıç, Sara Şebnem; Etzioni, Amos; Freeman, Alexandra F.; Thiel, Jens; Schulze, Ilka; Al-Herz, Waleed; Metin, Ayse; Sanal, Oezden; Tezcan, Ilhan; Yeganeh, Mehdi; Niehues, Tim; Dueckers, Gregor; Weinspach, Sebastian; Patiroglu, Turkan; Ünal, Ekrem; Dasouki, Majed; Yılmaz, Mustafa; Genel, Ferah; Aytekin, Caner; Kütükçüler, Necil; Somer, Ayper; Kılıç, Mehmet; Reisli, Ismail; Camcioğlu, Yıldız; Gennery, Andrew R.; Cant, Andrew J.; Jones, Alison; Gaspar, Bobby H.; Arkwright, Peter D.; Pietrogrande, Maria C.; Baz, Zeina; Al-Tamemi, Salem; Lougaris, Vassilios; Lefranc, Gerard; Megarbane, Andre; Boutros, Jeannette; Galal, Nermeen; Bejaoui, Mohamed; Barbouche, Mohamed-Ridha; Geha, Raif S.; Chatila, Talal A.; Grimbacher, Bodo; KILIÇ GÜLTEKİN, SARA ŞEBNEM; Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik İmmünoloji Anabilim Dalı.; AAH-1658-2021
Background: Mutations in dedicator of cytokinesis 8 (DOCK8) cause a combined immunodeficiency (CID) also classified as autosomal recessive (AR) hyper-IgE syndrome (HIES). Recognizing patients with CID/HIES is of clinical importance because of the difference in prognosis and management.Objectives: We sought to define the clinical features that distinguish DOCK8 deficiency from other forms of HIES and CIDs, study the mutational spectrum of DOCK8 deficiency, and report on the frequency of specific clinical findings.Methods: Eighty-two patients from 60 families with CID and the phenotype of AR-HIES with (64 patients) and without (18 patients) DOCK8 mutations were studied. Support vector machines were used to compare clinical data from 35 patients with DOCK8 deficiency with those from 10 patients with AR-HIES without a DOCK8 mutation and 64 patients with signal transducer and activator of transcription 3 (STAT3) mutations.Results: DOCK8-deficient patients had median IgE levels of 5201 IU, high eosinophil levels of usually at least 800/mu L (92% of patients), and low IgM levels (62%). About 20% of patients were lymphopenic, mainly because of low CD4(+) and CD8(+) T-cell counts. Fewer than half of the patients tested produced normal specific antibody responses to recall antigens. Bacterial (84%), viral (78%), and fungal (70%) infections were frequently observed. Skin abscesses (60%) and allergies (73%) were common clinical problems. In contrast to STAT3 deficiency, there were few pneumatoceles, bone fractures, and teething problems. Mortality was high (34%). A combination of 5 clinical features was helpful in distinguishing patients with DOCK8 mutations from those with STAT3 mutations.Conclusions: DOCK8 deficiency is likely in patients with severe viral infections, allergies, and/or low IgM levels who have a diagnosis of HIES plus hypereosinophilia and upper respiratory tract infections in the absence of parenchymal lung abnormalities, retained primary teeth, and minimal trauma fractures.